The Molecular Libraries Screening Center Network (MSLCN) has been created by the NIH to serve as national resource with the following objectives: (1) To provide High Throughput Screening (HTS) capability to the problem of identifying small organic molecules (lead compounds) that are active in biological assays, (2) To apply the tools of synthetic chemistry to these leads in order to improve their utility as probes for studying biological systems both in vitro and in vivo, and (3) To make the compounds and associated information available to the public and private sectors as research tools, the information being accessible in a database to be known as PubChem. A strategic focus of the project is implementing HTS-based assays for classes of proteins within different gene families. To this end, we propose the following: I. To establish in accordance with the directives detailed in the MLSCN RFA-RM-04-017, a Duke University Molecular Libraries Screening Center (DMLSC) as an integral satellite member of the MLSCN. Our primary areas of focus would lie with the gene families represented by the orphan and identified Seven Transmembrane/G protein coupled receptors (7TM/GPCR) and their corresponding regulatory proteins. We would use for our primary HTS a high content imaging technology invented and patented by Duke Scientists. Within this thematic structure we have the following aims: (a) To develop the capability by the third quarter of Year 1 to process 10,000 compounds per week enabling a throughput of 10 or more assays per year by the end of the fourth quarter, (b)To have the capability by the end of the first quarter of Year 2 of the project to process 100,000 compounds per assay in two weeks, (c) To have the capability by the end of the first quarter of Year 3 of the project to process 100,000 compounds for separate assays every 2-2.5 weeks and (d) To develop the complementary capability to upload the associated assay data, including information describing lead compounds, to PubChem in a timely manner consistent with NIH guidelines. By accomplishing these aims a Duke screening Center will exceed the NIH assay throughput goal of screening 100,000 compounds in 20 separate assays per year and the associated goal of making compounds and information available to the public and private sectors as research tools. [unreadable] [unreadable] [unreadable]